To eluidate the role of osteopontinm, we prepared to examine the effect of osteopontin overexpression as well as inactivation of osteopontin gene in mice system. We first cloned murine osteopontin gene and constructed vectors by using the upstream exons. These constructs also contained neo-gene cassett and were introduced into murine ES cells by electroporation. ES cells containing homologous recombination in the osteopontin gene were selected and they were introduced into the blastocele. Chymeric mice were identified by their coat color and were mated to prodece mice which lack osteopontin gene through homolo gous recombination. With regard to over expression experiments, osteopontin gene was cloned down stream of a strong promoter to yield inducible expression vectors and this vector was introduced via microinjection into fertilized eggs which were subsequently implanted into the uterus of pseudo-pregnant mice.